Effects of anesthetics on diphenylhydantoin metabolism in the rat: possible inhibition by diethyl ether

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Abstract
The effects of diethyl ether and urethane on the elimination of diphenylhydantoin (DPH) in the rat were compared. The apparent half-life of DPH following a dose of 10 mg/kg, iv, under continuous ether anesthesia was 284 ± 47 min, while the half-life under urethane anesthesia was 25.5 ± 6.3 min. The latter was in agreement with the literature value for DPH half-life without anesthesia. The effects of both anesthetic agents on bile flow and indocyanine green clearance were not different. Following intravenous administration of DPH (1 mg/kg), DPH metabolites excreted in bile at 2 h were 75.3 ± 4.8% of the dose with urethane anesthesia and 25.0 ± 5.0% of the dose with continuous ether anesthesia. The data suggest that ether may inhibit the DPH metabolism in vivo, most likely at the hydroxylation step, while urethane does not.